Nature Structural & Molecular Biology Contents: 2014 Volume #21 pp 289-425

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TABLE OF CONTENTS April 2014 Volume 21, Issue 4 Focus Editorial Commentaries Reviews News and Views Articles Brief Communication Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement nature.com webcasts Macmillan Science Communication presents a custom webcast: The power of imaging flow cytometry in immunology. Tuesday April 22nd at 8am PDT / 11am EDT / 4pm BST / 5pm CEST  Register for the free webcast followed by a live Q & A session  Sponsored by:     Focus Top Focus on Ubiquitin Focus issue: April 2014 Volume 21 No 4 Contents Editorial Commentaries Reviews Sponsor Editorial Top Focus on Ubiquitin Essential modifications   p289 doi:10.1038/nsmb.2811 Ubiquitin and ubiquitin-like proteins have central roles in regulating cellular processes and homeostasis. This Focus examines our understanding of the ubiquitination reaction and the mechanisms by which ubiquitin and related modifications affect protein and cellular functions. Commentaries Top Focus on Ubiquitin Ubiquitin sets the timer: impacts on aging and longevity   pp290 - 292 Eva Kevei and Thorsten Hoppe doi:10.1038/nsmb.2806 Protein homeostasis is essential for cellular function, organismal growth and viability. Damaged and aggregated proteins are turned over by two major proteolytic routes of the cellular quality-control pathways: the ubiquitin-proteasome system and autophagy. For both these pathways, ubiquitination provides the recognition signal for substrate selection. This Commentary discusses how ubiquitin-dependent proteolytic pathways are coordinated with stress- and aging-induced signals. Focus on Ubiquitin Plant ubiquitin ligases as signaling hubs   pp293 - 296 Nitzan Shabek and Ning Zheng doi:10.1038/nsmb.2804 The past decade has witnessed an explosion in the identification of ubiquitin-ligase complexes as the missing receptors for important small-molecule hormones regulating plant growth and development. These breakthroughs were initiated by genetic approaches, with structural analysis providing mechanistic insights into how hormone perception and signaling are coupled to protein ubiquitination. Although there are still many unknowns, plants have imparted valuable lessons about the pharmacology of ubiquitin modification. Focus on Ubiquitin Ubiquitin in inflammation: the right linkage makes all the difference   pp297 - 300 Jacob E Corn and Domagoj Vucic doi:10.1038/nsmb.2808 The immune system must operate in an effective, precise and safe manner to defend against diverse pathogens while avoiding attacking the body itself and commensal bacteria. Inflammatory pathways mediated by NOD-like, Toll-like, RIG-I-like and tumor-necrosis-factor receptor families are tightly regulated by ubiquitination, especially by Lys63-linked and linear polyubiquitin chains. Here we discuss the human ubiquitin-mediated inflammatory signaling system, emphasizing the interactions and activities whose coordination ensures timely, accurate regulation of inflammatory responses. Reviews Top Focus on Ubiquitin New insights into ubiquitin E3 ligase mechanism   pp301 - 307 Christopher E Berndsen and Cynthia Wolberger doi:10.1038/nsmb.2780 Ubiquitin E3 ligases catalyze the final step of the ubiquitination cascade, promoting the transfer of ubiquitin from the E2 to the substrate target. Recent structural and biochemical studies have given insights in the catalytic mechanisms of all three E3 ligase classes, as discussed in this Review. Focus on Ubiquitin Lysine-targeting specificity in ubiquitin and ubiquitin-like modification pathways   pp308 - 316 Francesca Mattiroli and Titia K Sixma doi:10.1038/nsmb.2792 Ubiquitin and ubiquitin-like (UBL) modifications occur primarily on lysine residues of target proteins to stimulate downstream signals. This Review discusses current knowledge of lysine specificity in ubiquitin and UBL targeting, with particular focus on the systems in which a detailed mechanism of modification and downstream signaling has been validated biochemically. Focus on Ubiquitin Two-way communications between ubiquitin-like modifiers and DNA   pp317 - 324 Helle D Ulrich doi:10.1038/nsmb.2805 DNA metabolism is regulated by the ubiquitin and SUMO modifications, but DNA also influences whether and when these modifications occur. This Review describes the mutual interactions between DNA, ubiquitin and SUMO that occur in DNA-associated processes. Focus on Ubiquitin Cleaning up in the endoplasmic reticulum: ubiquitin in charge   pp325 - 335 John C Christianson and Yihong Ye doi:10.1038/nsmb.2793 The endoplasmic reticulum-associated degradation (ERAD) pathway maintains protein homeostasis in the ER by retrotranslocating unwanted proteins to the cytosol for proteasomal degradation. This Review discusses the integral role of the ubiquitin system in ERAD, highlighting how the two pathways intertwine to facilitate transport across the ER membrane. Focus on Ubiquitin Dynamic regulation of macroautophagy by distinctive ubiquitin-like proteins   pp336 - 345 Daniel J Klionsky and Brenda A Schulman doi:10.1038/nsmb.2787 Whereas the proteasome degrades individual proteins modified with ubiquitin chains, autophagy degrades many proteins and organelles en masse. A pair of ubiquitin-like proteins (UBLs), Atg8 and Atg12, regulate autophagy-mediated degradation in a manner completely distinct from that of ubiquitin in the proteasome pathway, as discussed in this Review. News and Views Top The JAMM in the proteasome   pp346 - 348 Tobias Wauer and David Komander doi:10.1038/nsmb.2800 Structures of the deubiquitinating enzyme Rpn11 of the proteasomal 19S regulatory particle reveal its role in hydrolyzing the proximal ubiquitin from a protein that is about to be degraded. RPA puts the brakes on MMEJ   pp348 - 349 Mitch McVey doi:10.1038/nsmb.2802 Microhomology-mediated end joining (MMEJ) is a mechanism of DNA double-strand-break repair that creates deletions and promotes other types of genome instability. New in vivo and in vitro analyses demonstrate that the heterotrimeric replication protein A (RPA) complex prevents spontaneous annealing of microhomologies, thereby preventing genome-destabilizing MMEJ. See also: Article by Deng et al. Promoter melting by an alternative σ, one base at a time   pp350 - 351 Seth A Darst, Andrey Feklistov and Carol A Gross doi:10.1038/nsmb.2798 Housekeeping σ factors are initiation factors for the bacterial RNA polymerase at most promoters, whereas alternative σs direct focused responses to specific environmental conditions. Structural and functional analysis of an alternative σ complexed with its cognate -10 motif elucidates the mechanism for initiation of strand opening, highlighting two critical properties: why alternative σs, compared to housekeeping σs, recognize so few promoters and how their promoter-recognition strategy was diversified during evolution. Structural & Molecular Biology JOBS of the week Molecular Biology Research Assistant State University of New York Professor Position in Molecular Biology University Paris-Sud International Max Planck PhD Program IMPRS for Molecular and Cellular Biology Max Planck Institute of Immunobiology and Epigenetics Postdoctoral Mount Sinai Medical Center/Icahn School of Medicine at Mount Sinai Post-Doctoral Research Associate position northewestern university More Science jobs from Structural & Molecular Biology EVENT Techniques & Applications of Molecular Biology 14.07.14 Coventry, UK More science events from Articles Top X-ray crystal structure of voltage-gated proton channel   pp352 - 357 Kohei Takeshita, Souhei Sakata, Eiki Yamashita, Yuichiro Fujiwara, Akira Kawanabe et al. doi:10.1038/nsmb.2783 Structural and functional analysis reveal the resting state of the voltage-gated proton channel Hv1. Comparison with structures of voltage-sensing domains from other systems, captured in the activated state, will aid in understanding the mechanism of voltage sensing. Global effects of the CSR-1 RNA interference pathway on the transcriptional landscape   pp358 - 365 Germano Cecere, Sebastian Hoersch, Sean O'Keeffe, Ravi Sachidanandam and Alla Grishok doi:10.1038/nsmb.2801 RNAi pathways inhibit gene expression at the transcriptional and post-transcriptional level. Genome-wide analyses of nascent RNA transcripts in nematodes now suggest that the CSR-1 RNAi pathway helps maintain the directionality of active transcription and propagate the distinction between transcriptionally active and silent genomic regions. Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks   pp366 - 374 François Aymard, Beatrix Bugler, Christine K Schmidt, Emmanuelle Guillou, Pierre Caron et al. doi:10.1038/nsmb.2796 DNA double-strand breaks (DSBs) may be repaired either by homologous recombination (HR) or nonhomologous end joining (NHEJ) pathways. A new high-resolution mapping study of DSBs in human cells shows that trimethylated histone H3 K36, a marker of active chromatin, targets RAD51 to DSBs within transcribed regions to promote preferential HR-mediated repair at transcriptionally active loci. Structural basis of the proinflammatory signaling complex mediated by TSLP   pp375 - 382 Kenneth Verstraete, Loes van Schie, Laurens Vyncke, Yehudi Bloch, Jan Tavernier et al. doi:10.1038/nsmb.2794 Thymic stromal lymphopoietin (TSLP) is a cytokine critical for the development of chronic inflammatory disorders including asthma and atopic dermatitis. The structure of the ternary complex formed by TSLP and its coreceptors TSLPR and the interleukin-7 receptor reveal how TSLP is able to organize receptor-receptor contacts to facilitate intracellular signaling. Structural basis for pure antagonism of integrin αVβ3 by a high-affinity form of fibronectin   pp383 - 388 Johannes F Van Agthoven, Jian-Ping Xiong, José Luis Alonso, Xianliang Rui, Brian D Adair et al. doi:10.1038/nsmb.2797 Integrins are promising targets in the treatment of conditions that range from cancer to acute coronary syndromes. However, the partial agonism exhibited by RGD ligand–based drugs can result in life-threatening complications. A new study provides the structural basis for pure antagonism by a high-affinity integrin ligand and suggests a path to the design of safer integrin inhibitors. Ty3 reverse transcriptase complexed with an RNA-DNA hybrid shows structural and functional asymmetry   pp389 - 396 Elzbieta Nowak, Jennifer T Miller, Marion K Bona, Justyna Studnicka, Roman H Szczepanowski et al. doi:10.1038/nsmb.2785 A new study reports the first structure of a retrotransposon reverse transcriptase in complex with its cognate polypurine tract RNA-DNA hybrid. In contrast to its retroviral counterparts, Ty3 reverse transcriptase forms an asymmetric homodimer that forms in the presence of substrate, with its RNase H and DNA polymerase activities likely contributed by separate subunits. Human immunoglobulin E flexes between acutely bent and extended conformations   pp397 - 404 Nyssa Drinkwater, Benjamin P Cossins, Anthony H Keeble, Michael Wright, Katharine Cain et al. doi:10.1038/nsmb.2795 IgE molecules associate with the FcεRIα receptor in an acutely bent conformation where the Cε2 domains fold over the Cε3-Cε4 domains. A new study demonstrates that IgE can exist in an extended conformation with a Cε2 domain capable of flipping from side to side, suggesting a level of structural flexibility that could functionally impact allergen recognition. RPA antagonizes microhomology-mediated repair of DNA double-strand breaks   pp405 - 412 Sarah K Deng, Bryan Gibb, Mariana Justino de Almeida, Eric C Greene and Lorraine S Symington doi:10.1038/nsmb.2786 Resection of DNA double strand–break ends generates single strands that can spontaneously anneal to undergo mutagenic microhomology-mediated end joining (MMEJ). A combination of genetic and biophysical assays now shows that replication protein A (RPA) thwarts strand annealing by binding to the resected ends to promote Rad51 filament assembly and error-free repair by homologous recombination. See also: News and Views by McVey Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and downstream effectors   pp413 - 422 David J Kast, Changsong Yang, Andrea Disanza, Malgorzata Boczkowska, Yadaiah Madasu et al. doi:10.1038/nsmb.2781 IRSp53 is a BAR-domain protein under the control of Rho family GTPases and has crucial roles in processes such as cell motility and tumor invasiveness. In a new study, IRSp53 is shown to be autoinhibited and is synergistically activated by the combinatorial action of Cdc42 and the tumor-promoting factor Eps8. Brief Communication Top The retrovirus HERVH is a long noncoding RNA required for human embryonic stem cell identity   pp423 - 425 Xinyi Lu, Friedrich Sachs, LeeAnn Ramsay, Pierre-Étienne Jacques, Jonathan Göke et al. doi:10.1038/nsmb.2799 Human endogenous retrovirus subfamily H (HERVH) is a class of transposable elements expressed preferentially in human embryonic stem cells (hESCs). A new study now shows that the long terminal repeats of HERVH function as enhancers and that HERVH is a nuclear long noncoding RNA required to maintain hESC identity. Top Advertisement FREE eBook: Key Advances in Medicine  An essential resource for anyone with an interest in medicine, 45 articles summarise the groundbreaking clinical studies of 2013 and highlight trends to watch out for in 2014.  Download FREE PDF now!    Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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